Key result
Brugada syndrome links to altered PBMC gene expression and protein sialylation correlating with phenotypic expression.
Why the study?
The role of post-translational modifications such as sialylation in Brugada Syndrome remains unknown despite its impact on voltage-gated channel activity.
Case-Control (n=84)
Dysregulation of the sialylation machinery in PBMCs of Brugada Syndrome patients correlates with clinical phenotype and may serve as a systemic biomarker.
May support PBMC sialylation as a Brugada biomarker; hypothesis-generating and requires prospective validation.
Brugada Syndrome (BrS) is an inherited arrhythmogenic disorder with an increased risk of sudden cardiac death. Recent evidence suggests that BrS should be considered as an oligogenic or polygenic condition. Mutations in genes associated with BrS are found in about one-third of patients and they mainly disrupt the cardiac sodium channel NaV1.5, which is considered the main cause of the disease. However, voltage-gated channel’s activity could be impacted by post-translational modifications such as sialylation, but their role in BrS remains unknown. Thus, we analyzed high risk BrS patients (n = 42) and healthy controls (n = 42) to assess an involvement of sialylation in BrS. Significant alterations in gene expression and protein sialylation were detected in Peripheral Blood Mononuclear Cells (PBMCs) from BrS patients. These changes were significantly associated with the phenotypic expression of the disease, as the size of the arrhythmogenic substrate and the duration of epicardial electrical abnormalities. Moreover, protein desialylation caused a reduction in the sodium current in an in vitro NaV1.5-overexpressing model. Dysregulation of the sialylation machinery provides definitive evidence that BrS affects extracardiac tissues, suggesting an underlying cause of the disease. Moreover, detection of these changes at the systemic level and their correlation with the clinical phenotype hint at the existence of a biomarker signature for BrS.
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Ghiroldi et al. (2022) conducted a case-control in Brugada Syndrome (n=84). Brugada Syndrome vs. Healthy controls was evaluated on Alterations in gene expression and protein sialylation in Peripheral Blood Mononuclear Cells (PBMCs). Brugada Syndrome patients exhibited significant alterations in gene expression and protein sialylation in PBMCs compared to healthy controls, correlating with phenotypic expression.
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